Aging and menopause reprogram osteoclast precursors for aggressive bone resorption
Open accessAbstract
Women gradually lose bone from the age of ~35 years, but around menopause, the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels, rendering these individuals more prone to developing osteoporosis. The increased osteoclast activity has been linked to a reduced estrogen level and other hormonal changes. However, it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast activity. Therefore, we set up a protocol in which CD14 + blood monocytes were isolated from 49 female donors (40–66 years old). Cells were differentiated into osteoclasts, and data on differentiation and resorption activity were collected. Using multiple linear regression analyses combining in vitro and in vivo data, we found the following: (1) age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro; (2) the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro; (3) the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause; and (4) the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with age. We conclude that monocytes are “reprogrammed” in vivo, allowing them to “remember” age, the menopausal status, and the bone formation status in vitro, resulting in more aggressive osteoclasts. Our discovery suggests that this may be mediated through DNA methylation. We suggest that this may have clinical implications and could contribute to understanding individual differences in age- and menopause-induced bone loss.
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Fusion of the earliest osteoclast precursors into multinucleated mature osteoclasts is a critical process in osteoclastogenesis, as the number of nuclei per cell determines osteoclast aggressiveness.
“The fusion of the earliest osteoclast precursors into multinucleated, mature osteoclasts is a critical process in osteoclastogenesis, as the number of nuclei per cell determines osteoclast aggressiveness.154”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [154]
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Proteomics of Human Bone Tissue Reveals Potential Key Molecules in OsteoporosisPreprint
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- Authors
- Møller, A. M. J., Delaissé, J.-M., Olesen, J. B., Madsen, J. S., Canto, L. M., Bechmann, T., Rogatto, S. R., & Søe, K.
- Affiliations
- University of Southern Denmark (DK)
- Odense University Hospital (DK)
- Vejle Sygehus (DK)
- Corresponding author
- Møller, Anaïs Marie Julie
- Søe, Kent
- Venue
- Bone Research
- Published
- 2020-07-01
- Volume
- 8
- Issue
- 1
- Pages
- 27-27
- ISSN
- 2095-4700 (ISSN-L)
- 2095-6231
- PMC
- PMC7329827
- OpenAlex
- W2997538246
- Cited by
- 6
- References
- 74
- Citations by year
- 2024: 1 · 2022: 3 · 2021: 2
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Bone Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Journal of Bone and Mineral Research
- Funders
- Syddansk Universitet
- Sygehus Lillebælt
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- menopause, aging, osteoclast precursors, bone resorption, osteoporosis, CD14+ monocytes, osteoclastogenesis, cathepsin K, DNA methylation, type I procollagen N-terminal propeptide, estrogen deficiency, bone loss
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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